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Relativistic jets are observed throughout the Universe and strongly affect their surrounding environments on a range of physical scales, from Galactic binary systems 1 to galaxies and clusters of galaxies 2 . All types of accreting black hole and neutron star have been observed to launch jets 3 , with the exception of neutron stars with strong magnetic fields 4,5 (higher than 10 12 gauss), leading to the conclusion that their magnetic field strength inhibits jet formation 6 . However, radio emission recently detected from two such objects could have a jet origin, among other possible explanations 7,8 , indicating that this long-standing idea might need to be reconsidered. But definitive observational evidence of such jets is still lacking. Here we report observations of an evolving jet launched by a strongly magnetized neutron star accreting above the theoretical maximum rate given by the Eddington limit. The radio luminosity of the jet is two orders of magnitude fainter than those seen in other neutron stars with similar X-ray luminosities 9 , implying an important role for the properties of the neutron star in regulating jet power. Our result also shows that the strong magnetic fields of ultra-luminous X-ray pulsars do not prevent such sources from launching jets.

The receptor tyrosine kinase ErbB4 and its ligand trophic factors of the neuregulin (NRG) family have been associated with schizophrenia and other mental disorders in human genetic studies. In vivo studies in mice have shown how abnormal Nrg-ErbB4 signaling leads to deviant behaviors relevant to distinct aspects of schizophrenia, including hyperactivity, sensory gating deficits, working and spatial memory deficits and impaired social behavior. However, so far little is known on the role of ErbB4 in attention and inhibitory control, two aspects of executive functions that are impaired in schizophrenia. Here we investigated the effects of constitutive loss of ErbB4 in the central nervous system of mice on performance in a 5-choice serial reaction time task (5CSRTT) assessing attention and inhibitory control. In this task, ErbB4 -/- mice did not show deficits in various parameters of attention, and premature responses as measure of inhibitory control. Nonetheless, ErbB4 -/- mice recapitulated a specific set of behavioral phenotypes associated with schizophrenia, including a deficit in spatial learning and memory in the Barnes Maze and in contextual fear learning, and a trend for a deficit in sensorimotor gating. Furthermore, we investigated the effect of acute pharmacological inhibition of ErbB tyrosine kinase receptor using the pan-ErbB kinase inhibitor JNJ-28871063 (JNJ), in an automated version of the 5CSRTT. JNJ did not affect attention and inhibitory control. In conclusion, our data suggest no direct involvement of a classical Nrg-ErbB4 pathway in attention and inhibitory control in mice, while it confirms the involvement of this pathway in other domains relevant to schizophrenia., (© 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

The eclipses of certain types of binary millisecond pulsars (i.e. 'black widows' and 'redbacks') are often studied using high-time-resolution, 'beamformed' radio observations. However, they may also be detected in images generated from interferometric data. As part of a larger imaging project to characterize the variable and transient sky at radio frequencies <200 MHz, we have blindly detected the redback system PSR J2215+5135 as a variable source of interest with the Low-Frequency Array (LOFAR). Using observations with cadences of two weeks - six months, we find preliminary evidence that the eclipse duration is frequency dependent (∝ν -0.4 ), such that the pulsar is eclipsed for longer at lower frequencies, in broad agreement with beamformed studies of other similar sources. Furthermore, the detection of the eclipses in imaging data suggests an eclipsing medium that absorbs the pulsed emission, rather than scattering it. Our study is also a demonstration of the prospects of finding pulsars in wide-field imaging surveys with the current generation of low-frequency radio telescopes.

We report on the results of a search for radio transients between 115 and 190 MHz with the LOw-Frequency ARray (LOFAR). Four fields have been monitored with cadences between 15 min and several months. A total of 151 images were obtained, giving a total survey area of 2275 deg 2 . We analysed our data using standard LOFAR tools and searched for radio transients using the LOFAR Transients Pipeline. No credible radio transient candidate has been detected; however, we are able to set upper limits on the surface density of radio transient sources at low radio frequencies. We also show that low-frequency radio surveys are more sensitive to steep-spectrum coherent transient sources than GHz radio surveys. We used two new statistical methods to determine the upper limits on the transient surface density. One is free of assumptions on the flux distribution of the sources, while the other assumes a power-law distribution in flux and sets more stringent constraints on the transient surface density. Both of these methods provide better constraints than the approach used in previous works. The best value for the upper limit we can set for the transient surface density, using the method assuming a power-law flux distribution, is 1.3 × 10 -3  deg -2 for transients brighter than 0.3 Jy with a time-scale of 15 min, at a frequency of 150 MHz. We also calculated for the first time upper limits for the transient surface density for transients of different time-scales. We find that the results can differ by orders of magnitude from previously reported, simplified estimates.

Background: A deficit in impulse control is a prominent, heritable symptom in several psychiatric disorders, such as addiction, attention-deficit/hyperactivity disorder, and schizophrenia. Here, we aimed to identify genes regulating impulsivity, specifically of impulsive action, in mice., Methods: Using the widely used 5-choice serial reaction time task, we measured impulsive action in 1) a panel of 41 BXD recombinant inbred strains of mice (n = 13.7 ± .8 per strain; n = 654 total) to detect underlying genetic loci; 2) congenic mice (n = 23) to replicate the identified locus; 3) mice overexpressing the Nrg3 candidate gene in the medial prefrontal cortex (n = 21); and 4) a Nrg3 loss-of-function mutant (n = 59) to functionally implicate the Nrg3 candidate gene in impulsivity., Results: Genetic mapping of impulsive action in the BXD panel identified a locus on chromosome 14 (34.5-41.4 Mb), syntenic with the human 10q22-q23 schizophrenia-susceptibility locus. Congenic mice carrying the impulsivity locus (Impu1) confirmed its influence on impulsive action. Increased impulsivity was associated with increased Nrg3 gene expression in the medial prefrontal cortex (mPFC). Viral overexpression of Nrg3 in the mPFC increased impulsivity, whereas a constitutive Nrg3 loss-of-function mutation decreased it., Conclusions: The causal relation between Nrg3 expression in the mPFC and level of impulsive action shown here provides a mechanism by which polymorphism in NRG3 in humans contributes to a specific cognitive deficit seen in several psychiatric diseases, such as addiction, attention-deficit/hyperactivity disorder, and schizophrenia., (Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

A new embolus detection system (EDS) is presented, built with the intention of detecting ongoing cerebral embolization in patients at risk of transient ischaemic attacks or stroke. It is based on the analysis of the audio-Doppler signal of a transcranial Doppler machine. The algorithm of the EDS estimates the intensity, duration and zero-crossing dynamics of the audio signal. The EDS has a multi-layer neural network which classifies events into micro-emboli signals (MES) or artefacts. The decision-making component of the software has been validated against human experts. Data from patients in the post-operative phase of carotid surgery were used for the validation process. The results showed agreement in MES and artefact classification of > 93%. Apart from a monitoring display, the monitoring system includes a verification unit that allows the user to listen and to look at all data of individual MES and artefacts. Moreover, the system allows the user to record, store and re-calculate all data files. Data are stored using European Data Format, which allows data transportation over the Internet. The EDS may have a potential in stroke risk stratification, evaluating the effect of novel anti-thrombotic therapies, and in peri-operative and remote monitoring of carotid endarterectomy.

Although disk accretion onto compact objects-white dwarfs, neutron stars and black holes-is central to much of high-energy astrophysics, the mechanisms that enable this process have remained observationally difficult to determine. Accretion disks must transfer angular momentum in order for matter to travel radially inward onto the compact object. Internal viscosity from magnetic processes and disk winds can both in principle transfer angular momentum, but hitherto we lacked evidence that either occurs. Here we report that an X-ray-absorbing wind discovered in an observation of the stellar-mass black hole binary GRO J1655 - 40 (ref. 6) must be powered by a magnetic process that can also drive accretion through the disk. Detailed spectral analysis and modelling of the wind shows that it can only be powered by pressure generated by magnetic viscosity internal to the disk or magnetocentrifugal forces. This result demonstrates that disk accretion onto black holes is a fundamentally magnetic process.

Fibroblast activation protein alpha (FAPalpha) is highly expressed in epithelial cancers and has been implicated in extracellular matrix remodeling, tumor growth, and metastasis. We present the first high resolution structure for the apoenzyme as well as kinetic data toward small dipeptide substrates. FAPalpha exhibits a dipeptidyl peptidase IV (DPPIV)-like fold, featuring an alpha/beta-hydrolase domain and an eight-bladed beta-propeller domain. Known DPPIV dipeptides are cleaved by FAPalpha with an approximately 100-fold decrease in catalytic efficiency compared with DPPIV. Moreover, FAPalpha, but not DPPIV, possesses endopeptidase activity toward N-terminal benzyloxycarbonyl (Z)-blocked peptides. Comparison of the crystal structures of FAPalpha and DPPIV revealed one major difference in the vicinity of the Glu motif (Glu(203)-Glu(204) for FAPalpha; Glu(205)-Glu(206) for DPPIV) within the active site of the enzyme. Ala(657) in FAPalpha, instead of Asp(663) as in DP-PIV, reduces the acidity in this pocket, and this change could explain the lower affinity for N-terminal amines by FAPalpha. This hypothesis was tested by kinetic analysis of the mutant FAPalpha/A657D, which shows on average an approximately 60-fold increase in the catalytic efficiency, as measured by k(cat)/K(m), for the cleavage of dipeptide substrates. Furthermore, the catalytic efficiency of the mutant is reduced by approximately 350-fold for cleavage of Z-Gly-Pro-7-amino-4-methylcoumarin. Our data provide a clear understanding of the molecular determinants responsible for the substrate specificity and endopeptidase activity of FAPalpha.

The relativistic plasma flows onto neutron stars that are accreting material from stellar companions can be used to probe strong-field gravity as well as the physical conditions in the supra-nuclear-density interiors of neutron stars. Plasma inhomogeneities orbiting a few kilometres above the stars are observable as X-ray brightness fluctuations on the millisecond dynamical timescale of the flows. Two frequencies in the kilohertz range dominate these fluctuations: the twin kilohertz quasi-periodic oscillations (kHz QPOs). Competing models for the origins of these oscillations (based on orbital motions) all predict that they should be related to the stellar spin frequency, but tests have been difficult because the spins were not unambiguously known. Here we report the detection of kHz QPOs from a pulsar whose spin frequency is known. Our measurements establish a clear link between kHz QPOs and stellar spin, but one not predicted by any current model. A new approach to understanding kHz QPOs is now required. We suggest that a resonance between the spin and general relativistic orbital and epicyclic frequencies could provide the observed relation between QPOs and spin.

Millisecond pulsars are neutron stars that are thought to have been spun-up by mass accretion from a stellar companion. It is not known whether there is a natural brake for this process, or if it continues until the centrifugal breakup limit is reached at submillisecond periods. Many neutron stars that are accreting mass from a companion star exhibit thermonuclear X-ray bursts that last tens of seconds, caused by unstable nuclear burning on their surfaces. Millisecond-period brightness oscillations during bursts from ten neutron stars (as distinct from other rapid X-ray variability that is also observed) are thought to measure the stellar spin, but direct proof of a rotational origin has been lacking. Here we report the detection of burst oscillations at the known spin frequency of an accreting millisecond pulsar, and we show that these oscillations always have the same rotational phase. This firmly establishes burst oscillations as nuclear-powered pulsations tracing the spin of accreting neutron stars, corroborating earlier evidence. The distribution of spin frequencies of the 11 nuclear-powered pulsars cuts off well below the breakup frequency for most neutron-star models, supporting theoretical predictions that gravitational radiation losses can limit accretion torques in spinning up millisecond pulsars.

We have detected, at x-ray and radio wavelengths, large-scale moving jets from the microquasar XTE J1550-564. Plasma ejected from near the black hole traveled at relativistic velocities for at least 4 years. We present direct evidence for gradual deceleration in a relativistic jet. The broadband spectrum of the jets is consistent with synchrotron emission from high-energy (up to 10 tera-electron volts) particles that were accelerated in the shock waves formed within the relativistic ejecta or by the interaction of the jets with the interstellar medium. XTE J1550-564 offers a rare opportunity to study the dynamical evolution of relativistic jets on time scales inaccessible for active galactic nuclei jets, with implications for our understanding of relativistic jets from Galactic x-ray binaries and active galactic nuclei.

We report on the rapid X-ray variability of the variable star and X-ray transient V4641 Sagittarii (SAX J1819.3-2525 = XTE J1819-254) as observed on 1999 September 15 by the proportional counter array (PCA) on board the Rossi X-Ray Timing Explorer. During the first approximately 900 s of the first PCA observation, V4641 Sgr showed very strong X-ray fluctuations by a factor of 4 on timescales of seconds to about 500 on timescales of minutes. The spectrum of the source during this flaring episode became harder when the count rate decreased. After this flaring episode, V4641 Sgr entered a quiescent state in which it remained for the rest of this and subsequent PCA observations. The X-ray spectrum was considerably softer in this quiescent state than during the flaring episode. The intrinsic X-ray luminosity (during both the flaring episode and the quiescent state) and the rapid X-ray variability do not strongly constrain the nature of the compact object (neutron star or black hole) in the system, although a black hole seems to be more likely. The very short duration of the bright X-ray phase of V4641 Sgr and its likely close proximity suggest that many similar objects could be present in our Galaxy, most of which are not noticed when they are in outburst because of the short duration of these outbursts. A considerable number of the black holes present in our Galaxy might be contained in systems similar to V4641 Sgr.

We present a study of the complex phase-lag behavior of the low-frequency (<20 Hz) quasi-periodic oscillations (QPOs) in the X-ray transient and black hole candidate XTE J1550-564 during its very high state. We distinguish two different types of low-frequency QPOs, based on their coherence and harmonic content. The first type is characterized by a 6 Hz QPO with a Q (the QPO frequency divided by the QPO width) of less than 3 and with a harmonic at 12 Hz. The second type of QPO is characterized by a 6 Hz QPO with a Q-value of greater than 6 and with harmonics at 3, 12, 18, and possibly at 9 Hz. Not only are the Q-values and the harmonic content of the two types different, but their phase-lag behavior also differs. For the first type of QPO, the low-energy photons (<5 keV) of both the 6 Hz QPO and its harmonic at 12 Hz lag the hard energy photons (>5 keV) by as much as 1.3 rad. The phase lags of the second type of QPO are more complex. The soft photons (<5 keV) of the 3 and 12 Hz QPOs lag the hard photons (>5 keV) by as much as 1.0 rad. However, the soft photons of the 6 Hz QPO precede the hard ones by as much as 0.6 rad. This means that different harmonics of this type of QPO have different signs for their phase lags. This unusual behavior is hard to explain when the lags are due to light-travel time differences between the photons at different energies, e.g., in a Comptonizing region surrounding the area in which the QPOs are formed.

The effects of altered terminal sequences in human chorionic gonadotropin (hCG) N- and O-linked glycans on receptor binding and signal transduction were analyzed using forms of hCG with remodelled carbohydrate chains. hCG derivatives were obtained by enzymic removal of the alpha 3-linked sialic acid residues followed by alpha 6-sialylation, alpha 3-galactosylation or alpha 3-fucosylation of uncovered Gal beta 1-->4GlcNAc (LacNAc) termini, or alpha 3-sialylation of Gal beta 1-->3GalNAc sequences. Also a form that carried GalNAc beta 1-->4-GlcNAc units, which are typical for pituitary hormone oligosaccharides, was derived by enzymic desialylation and degalactosylation followed by beta 4-N-acetylgalactosaminylation. The potency to stimulate testosterone production and the binding to the lutotropin/choriogonadotropin receptor of the preparations were compared with those of native and desialylated hCG (as-hCG). The decrease in bioactivity caused by desialylation of hCG was only restored upon alpha 6-sialylation of the Gal beta 1-->4GlcNAc beta 1-->-2Man alpha 1-->3Man branch of the N-linked glycans. This was without a major effect on receptor binding. Further alpha 6-sialylation, occurring at the Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->6Man branch, resulted in a bioactivity below a level found with as-hCG, concomitant with a decreased receptor binding affinity. Similarly alpha 3-galactosylation of the Gal beta 1-->4GlcNAc beta 1-->2-Man alpha 1-->6Man branch yielded a hCG derivative that showed decreased bioactivity and receptor binding. alpha 3-Fucosylation of native as well as as-hCG also led to a decreased activity. Re-alpha 3-sialylation of the O-linked chains on as-hCG had little effect on the bioactivity and receptor binding. Hormone preparations with GalNAc beta 1-->4GlcNAc termini showed lower bioactivity and receptor affinity than as-hCG. It is concluded that the Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->3Man- rather than the Gal beta 1-->4GlcNAc beta 1-->2-Man alpha 1-->6Man branch of the N-linked glycans on hCG plays an essential role in signal transduction, whereas the latter branch can potentially interfere with receptor binding. Furthermore attachment of sialic acid, but not of other sugars, to the first branch fulfils the requirement for the full expression of bioactivity, while sialylation of the O-linked chains is of minor importance.

Human chorionic gonadotrophin (hCG) is a heterodimeric glycoprotein hormone consisting of an alpha- and a beta-subunit, both containing two N-linked, complex-type glycans. Using this hormone as a model glycoprotein, the influence of its polypeptide part on the activity and specificity of bovine colostrum CMP-NeuAc:Gal beta 1----4GlcNAc-R alpha 2----6-sialyltransferase (alpha 6-sialyltransferase) was investigated. Initial rates of sialic acid incorporation into the desialylated glycans of hCG alpha and hCG beta in the heterodimer were higher with the alpha-subunit. This appeared to be due to a higher V which, together with a slightly lowered affinity (higher Km), resulted in a higher kinetic efficiency of the sialyltransferase for the glycans of this subunit. By contrast, the kinetic parameters did not differ significantly when the subunits were in the free form, indicating that the differences in the kinetics of sialylation found for the subunits in the heterodimeric state were not caused by the differences in N-linked carbohydrate structures of the subunits. It is proposed that these effects are due to conformational constraints which the polypeptide moieties put on the glycan chains upon dimerization. Furthermore, it was investigated whether the polypeptide of hCG would interfere with the sialyltransferase so as to alter the branch specificity of the enzyme. 1H-NMR spectroscopy (400 MHz) of the glycan chains, alpha 6-sialylated in vitro, showed that the enzyme highly prefers the galactosyl residue at the Gal beta 1----4GlcNAc beta 1----2-Man alpha 1----3Man branch for attachment of the first mol of sialic acid into the diantennary glycans of desialylated hCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Biologically active recombinant human follitropin has been expressed in Chinese hamster ovary cells. The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. The oligosaccharides were separated from the N-deglycosylated protein by gel-permeation chromatography on Bio-Gel P-100, and fractionated by a combination of FPLC on Mono Q and HPLC on Lichrosorb-NH2. The structures of the carbohydrate chains were determined by 500- or 600-MHz 1H-NMR spectroscopy. The following types of carbohydrates occur: monosialylated diantennary (10%), disialylated diantennary (43%), disialylated tri-antennary (5%), trisialylated tri-antennary (13%), trisialylated tri'-antennary (8%), and tetrasialylated tetraantennary (12%) N-acetyllactosamine type of carbohydrate chains, all bearing exclusively alpha 2-3-linked N-acetylneuraminic acid (Neu5Ac). Previously, for pituitary follitropin mono-, di-, tri-, tri'-, and tetra-antennary oligosaccharides containing alpha 2-3- as well as alpha 2-6-linked Neu5Ac residues were reported. The bisecting GlcNAc residues present in native follitropin were not detected in the recombinant glycoprotein. Of the oligosaccharides 29% have an alpha 1-6-linked Fuc residue at the asparagine-bound GlcNAc, whereas this amount is about 50% in pituitary follitropin. In some of the tri-, tri'- and tetra-antennary oligosaccharide fractions small amounts (less than 5%) of compounds were detected having one or more additional N-acetyllactosamine units.

The flavoprotein p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens was modified by several arginine-specific reagents. Modifications by 2,3-butanedione led to the loss of activity of the enzyme, but the binding of p-hydroxybenzoate and NADPH to the enzyme was little or not at all affected. However the formation of the enzyme-substrate complex of the modified enzyme was accompanied by an increase of the fluorescence of protein-bound FAD, in contrast to that of native enzyme which leads to quenching of the fluorescence. Enzyme modified by phenylglyoxal did not bind p-hydroxybenzoate nor NADPH. Quantification and protection experiments showed that two arginine residues are essential and a model is described which accounts for the results. Modification by 4-hydroxy-3-nitrophenylglyoxal reduced the affinity of the enzyme for the substrate and NADPH. The ligands offered no protection against inactivation. From this it is concluded that one arginine residue is essential at some stage of the catalysis. This residue is not associated with the substrate- or NADPH-binding site of the enzyme. Time-resolved fluorescence studies showed that the average fluorescence lifetime and the mobility of protein-bound FAD are affected by modification of the enzyme.

p-Hydroxybenzoate hydroxylase was modified by diethyl pyrocarbonate at pH values greater than 7 and by p-diazobenzoate. Modification of the enzyme by diethyl pyrocarbonate abolishes the affinity of the enzyme for the substrate p-hydroxybenzoate. Modification by p-diazobenzoate has the same effect on the enzyme. The enzyme is protected against these modifications by the effector p-fluorobenzoate. The data indicate that the modification of one tyrosine residue in the active center of the enzyme is responsible for the loss of enzyme activity. This tyrosine residue has been identified by sequence studies using radioactively labeled p-diazobenzoate and was found to be most probably Tyr-222. Diethyl pyrocarbonate reacts with a tyrosine residue in the active center other than Tyr-222; the former could not be identified. Sequence studies further showed that Cys-211 is also partially modified by p-diazobenzoate. In addition, the sequence of residues 343-345 was found to be Ser-Trp-Trp instead of the tentative assignment Ser-Tyr-Trp made earlier. The results are briefly discussed on the basis of the existing three-dimensional model of the enzyme.

The function of ribosomal protein S21 in protein synthesis has been examined by (a) inactivation of S21 in situ with specific antibodies and (b) the use of 30-S subunits reconstituted in the absence of S21. The results from the two approaches are consistent, 30-S subunits treated with anti-S21 or lacking S21 are still active in the translation of poly(U) or poly(A, G, U). They are also functional in fMet-tRNA binding when directed by poly(A, G, U) or the AUG triplet. They are not active in the translation of MS2 RNA or Escherichia coli mRNA. The defect of S21-deficient 30-S ribosomes can be traced back to their inability to bind MS2 RNA at the initiation step of protein synthesis. Addition of S21 to S21-deprived subunits restores the MS2-RNA-dependent initiation complex formation.

The flavoprotein p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens is inactivated by diethyl pyrocarbonate. Below pH 7, diethyl pyrocarbonate reacts specifically with histidine residues. The inactivation reaction is biphasic and follows pseudo-first-order kinetics. Four of the nine histidine residues of the enzyme are modified. During the first phase of the reaction, one histidine residue is modified and leads to a loss of about 30% of the activity. Modification of the additional three histidine residues during the second phase leads to complete loss of activity. Two of the latter histidine residues are essential for activity and are involved in the binding of reduced nicotinamide adenine dinucleotide phosphate (NADPH). The activity can be restored almost quantitatively upon treatment of modified enzyme with hydroxylamine. The modified enzyme is still capable of binding NADPH. The dissociation constant of the enzyme-NADPH complex is larger by a factor of 10 for the modified enzyme as compared to that for the native enzyme. The modification does not affect the affinity of the enzyme for the substrate, although effectors protect two histidine residues from chemical modification by diethyl pyrocarbonate. The rate of inactivation of the enzyme is pH dependent and increases with increasing pH values. From the pH dependence of the rate constant, it is calculated that two cooperative histidine residues participate in the reaction with diethyl pyrocarbonate. Both histidine residues possess a pKa' value of 6.2. At pH greater than 7, other reactions take place which are completely abolished in the presence of an effector (substrate) of the enzyme.

NADPH binding to p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens is found to be strongly dependent on pH and ionic strength. In the ionic strength range of 0.02-0.15 M, optimal NADPH binding is observed at a pH value of 6.4. Extrapolation of the dissociation constants to infinite ionic strength shows that under these conditions optimal binding occurs at pH values greater than 8. Similar results were obtained for complexes between the enzyme and two NADPH analogues in the presence or absence of the substrate. The experimental data can be explained by a theoretical model in which monopole-monopole or monopole-dipole interactions between the enzyme and the ligand are dominant. Changes in the former interaction prevail at low ionic strength and low pH values while the changes in the latter prevail at high ionic strength and high pH values. The dipole moment of the enzyme in the direction of the NADPH binding site was calculated from the ionic strength and pH dependence of the complex formation. The calculated dipole moment of the enzyme is about 2000 Debye at pH 6 and decreases to about 1100 Debye at pH 8.5. The results are discussed with respect to published results, including data obtained from the enzyme from a different source.